The 1-(p-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline (EP O 283 848 A1 [1988]): ##STR1## is an intermediate in the synthesis of compounds with morphinan type structure (Grewe, R.; Friedrichsen, W. Chem.Ber. 1967, 100, 1550.) The (-) enantiomer of I can be converted to dextromethorphan (Ger. Pat. 1795193 C2 (1971)), an important commercial antitussive agent. The (+) enantiomer can be used in the synthesis of levallorphan, a narcotic antagonist (Schneider, O.; Gruessner, D. Helv.Chim.Acta 1951 34,2211) or butorphanol, an analgesic (Ger. Pat. 2,2243, 961 (1973)).
When dextromethorphan is the target of the synthesis, the racemic I is subjected to enantiomeric resolution and the (-) enantiomer is converted to dextromethorphan. Usually, the enantiomeric resolution of I is done using diastereomeric salt precipitation with (-)-mandelic acid. The isolated material in the resolution step has an enantiomeric excess (ee) of 98-99% in (-) isomer. Left behind is a mixture which has a 60 to 70% ee in (+) isomer. Critical for the economics of the process is the recycling of this mixture. This is done by racemization of the (+) isomer, a chemically destructive process run under harsh conditions.
The object of this invention is a process of separation of the (-) enantiomer of I in which, in the recycling of the mixture after the separation of (-)-I, using (-)-mandelic acid, racemic I is isolated, and only (+)-I with ee of about 93-94% is subjected to the harsh, destructive conditions of the racemization step.
This and other objections of the invention will be apparent to one skilled in the art after review of the following description of the invention.